Atopic Dermatitis Peer-to-Peer Educational Toolkit - PowerPoint Presentation

Slide1

Atopic Dermatitis Peer-to-Peer Educational Toolkit

Lawrence A. Schachner, M.D

Professor, Chair Emeritus and

Stiefel

Laboratories ChairDirector of the Division of Pediatric Dermatology Department of Dermatology & Cutaneous Surgery Professor, Department of PediatricsLeonard M. Miller School of MedicineUniversity of Miami

Leon H. Kircik M.D.Clinical Associate Professor of Dermatology Indiana University School of MedicineMount Sinai Medical Center, New York, NY Physicians Skin Care, PLLCLouisville, KY

David E. Cohen, M.D., M.P.H.Charles and Dorothea Harris Professor and Vice Chairman for Clinical AffairsDirector of Allergic, Occupational and Environmental DermatologyNew York University School of Medicine Department of Dermatology

Fernanda Bellodi Schmidt, MDAssistant ProfessorDepartment of Dermatology and Cutaneous SurgeryUniversity of Miami Health Systems

A compilation of key content from select presentations at the 2020 South Beach Symposium and the Masters of Pediatric Dermatology

Slide2

Silverberg J, et al. EADV 2018, FC01.01. Sponsored by Pfizer

All ages (0–18+)

0–4%

5–8%

9–12%13–16%

Canada9%Mexico12%USA9%Brazil

11%UK10%

France7%Spain

11%

Switzerland

5%

Germany

6%

Turkey

12%

Israel

3%

Italy

8%

Australia

10%

Saudi Arabia

10%

Taiwan

9%

Japan

6%

South Korea

14%

China

14%

A global epidemiology survey of the prevalence and severity of AD: All patients

David E. Cohen, M.D.

Slide3

Hannifin Criteria: Major criteria (need 3 or more) are as follows:

J

Dermatol

. 2016 Apr;43(4):376-84. doi: 10.1111/1346-8138.13264.David E. Cohen, M.D.

Slide4

Hannifin Criteria: Minor criteria (need 3 or more) are as follows:

J

Dermatol

. 2016 Apr;43(4):376-84. doi: 10.1111/1346-8138.13264.David E. Cohen, M.D.

Slide5

Guidelines for the management of atopic dermatitis – Diagnosis and Assessment

J

Am

Acad Dermatol. 2014 Feb; 70(2): 338–351.David E. Cohen, M.D.

Slide6

Atopic Dermatitis

–

co-factors

Asthma

Eczema

AR

~33%

~33%

~38%

Expert Rev

Clin

Immunol. 2016 Jul 28:1-12. [

Epub

ahead of print]

Curr

Med Res

Opin

. 2016 Jun 21:1-7. [

Epub

ahead of print]

David E. Cohen, M.D.

Slide7

Two Major Hypotheses on

Development of Inflammation

Outside-Inside View

Inside-Outside View

David E. Cohen, M.D.

Slide8

Skin barrier – more than just “mortar and brick”

Fernanda Schmidt, M.D.

Slide9

Structural and functional differences

between infant and adult skin

Oranges T, Dini V,

Romanelli

MFernanda Schmidt, M.D.

Slide10

Immune pathways associated with AD

Clin Rev Allergy Immunol. 2020 Jan 9.

doi

: 10.1007/s12016-019-08775-4.Actas Dermosifiliogr. 2020 Jan 20.

pii: S0001-7310(19)30389-8.Experimental Dermatology, Volume: 28, Issue: 1, Pages: 3-10, First published: 17 October 2018, DOI: (10.1111/exd.13808) David E. Cohen, M.D.

Slide11

Emerging AD Treatments & Associated Pathways

Th22, Th17, and other intracellular processes

Fezankizumab

Secukinumab

PDETapinarofTh: T-helper cell; IL: interleukin; JAK: janus kinase; STAT: JAK/signal transducer and activator of transcriptionAnn Allergy Asthma Immunol 124 (2020): 28-35. doi: https://doi.org/10.1016/j.anai.2019.10.005David E. Cohen, M.D.

Slide12

Overall Summary of AD

David E. Cohen, M.D.

Slide13

Dupilumab – Caution Required

Leon H.

Kircik

M.D.

Slide14

Tralokinumab

Tralokinumab

is a fully human, immunoglobulin (Ig)G4 monoclonal antibody that potently and specifically binds to and neutralizes the effects of IL-13

1

1. Popovic et al. J Mol Biol 2017;429:208–219; 2. May et al. Br J Pharmacol 2012;166:177; 3. Thom et al. Methods Mol Biol 2012;805:393;4. Thom et al. PNAS 2006; 103 (20):76191-4Leon H. Kircik M.D.

Slide15

Tralokinumab

EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; TCS, topical corticosteroid

Adapted from

Wollenberg

et al. J Allergy Clin Immunol 2018, Article in press. DOI: 10.1016/j.jaci.2018.05.029.Tralokinumab improved the extent and severity of atopic dermatitisap-value for the adjusted mean difference compared with placebo; bp-value for the adjusted percentage difference compared with placeboLeon H. Kircik M.D.

Slide16

Lebrikizumab

Proportion of atopic dermatitis patients achieving (A) a 50% reduction of Eczema Area and Severity Index, (B) a 75% reduction of Eczema Area and Severity Index, (C) an Investigator Global Assessment of 0 or 1, and (D) a 50% reduction of

SCORing

Atopic Dermatitis at week 12 of lebrikizumab treatment. Q4W, Every 4 weeks; SD, single dose.

Leon H. Kircik M.D.

Slide17

JAK/STAT Signaling Pathways

BARICITINIB

"Lilly Announces Top-Line Phase 3 Results for Oral

Jak

Inhibitor Baricitinib, in Combination with Topical Corticosteroids in Adult Patients with Moderate to Severe Atopic Dermatitis." 2019. Print.Leon H. Kircik M.D.

Slide18

JAK/STAT Signaling Pathways

UPADICITINIB

Adapted from

Marjolein

S de Bruin-Weller presentation at 2018 International symposium on Atopic DermatitisLeon H. Kircik M.D.

Slide19

A Greater Proportion of Patients Achieved a Response

at Week 12 With the 100-mg and 200-mg

Doses

Primary End Point: IGA Responsea at Week 12* P = 0.0184** P = 0.0032

Placebo10 mg30 mg100 mg200 mgR

esponse6.3%8.2%12.3%

27.8%44.5%95% CI

-0.2-12.9

2.2-14.1

4.9-19.7

14.8-40.9

26.7-62.3

P

value

—

0.1210

0.1065

0.0184

0.0032

CI, confidence interval;

E

max

, the

difference between

maximum

achievable response (at infinite dose) and baseline; FAS, full analysis set;

IGA, Investigator’s

Global Assessment; NRI, nonresponder imputation; SE, standard

error.

a

Emax fitted

curve with

SE. Baseline was defined as last measurement before first dosing.

IGA

response was defined as a score of clear (0) or almost clear (1)

with

a ≥2-point improvement from baseline at week 12 (FAS, NRI). For discontinued subjects, any

missing

value for all subsequent

visits

until week 12 was imputed using

the

NRI

approach. Bars indicated

SE.

JAK/STAT Signaling Pathways

ABROCITINIB

Leon H.

Kircik

M.D.

Slide20

Phase

3 trial:

mEASI

and IGA responses with topical delgocitinib among patients with moderate to severe ADDelgocitinibPan-JAK inhibitionLeon H. Kircik M.D.

Slide21

Topical

Tapinarof

Therapeutic

Aryl Hydrocarbon Receptor Modulating Agent

Leon H. Kircik M.D.

Slide22

Atopic

Dermatitis

Lawrence Schachner M.D.

Slide23

Avoiding Treatment Pitfalls

Lawrence Schachner M.D.

Slide24

Severity

Topical Treatment

Schedule

If Severe:

Clobetasol (high potency CS) + TCI or PDI + emollientsTwice daily for 3-5 daysIf Moderate:Triamcinolone (medium potency CS) + TCI or PDI + emollientsTwice daily for 3-5 daysIf Mild:Alclometasone (low potency CS) + TCI or PDI + emollientsTwice daily for 3-5 daysControlled:TCI or PDI or TS + emollientsTwice daily for 2 weeksMaintenance (to areas of predilection):TCI or PDI or TS + emollientsTwice weekly for 6 monthsLong-term Maintenance & Prevention:EmollientsTwice daily

*Abbreviations: CS: Corticosteroid. PDI: Phosphodiesterase inhibitor. TCI: Topical Calcineurin Inhibitor

The Schachner LadderOberlin KE, Nanda S. Atopic dermatitis made easy: The Schachner Ladder. Pediatr Dermatol

. 2019;36(6):1017-8.Lawrence Schachner M.D.

Slide25

Algorithm For The Treatment Of Moderate To Severe Atopic Dermatitis

Lawrence Schachner M.D.

Slide26

Crisaborole

J

Pharmacol

Exp Ther. 2001;299:753-759Inflamm Allergy Drug Targets 2007 Mar;6(1):17-26.Lawrence Schachner M.D.

Slide27

Efficacy and safety of

crisaborole

ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults

Paller

et al. J Am Acad Dermal 2016;75:494-503Lawrence Schachner M.D.

Slide28

Dupilumab

Recently in May 2020, Dupilumab got FDA approval for the treatment of moderate to severe atopic dermatitis in children aged 6 to 11 years (POST 2020 MOPD)

Clark et al. Cutis.

2018 Sep;102(3):201-204.

Deleuran M, et al. J Am Acad Dermatol. 2020 Feb;82(2):377-88. Igelman S, et al. J Am Acad Dermatol. 2020 Feb;82(2):407-11.Lawrence Schachner M.D.

Slide29

Igelman

S, Kurta AO, Sheikh U, McWilliams A,

Armbrecht

E, Jackson

Cullison SR, et al. Off-label use of dupilumab for pediatric patients with atopic dermatitis: A multicenter retrospective review. J Am Acad Dermatol. 2020;82(2):407-11.Dupilumab: Safety and Efficacy StudiesLawrence Schachner M.D.